COMPARISON OF THE EFFECTS OF CARVEDILOL, PROPRANOLOL, AND VERAPAMIL ON INVITRO PLATELET-FUNCTION IN HEALTHY-VOLUNTEERS

The effects of the two beta-blockers carvedilol and propranolol and the calcium antagonist verapamil on platelet aggregation induced by ADP, epinephrine, or collagen was examined in the serum of eight healthy volunteers. The inhibitory potential of the three drugs on the arachidonic acid-prostaglandin pathway was measured by the assessment of the formation of the stable metabolite thromboxane B2. Furthermore, the influence of drugs on intracellular cAMP levels was measured in platelets aggregated with ADP, epinephrine, or collagen. All three drugs were able to inhibit platelet aggregation induced by a threshold concentration of ADP, epinephrine (10-mu-M), or collagen (1-mu-g/ml) in a concentration-dependent manner, preventing aggregation completely in the high micromolar range. Propranolol is 1.6 and 2.3 times more active than verapamil and carvedilol in inhibiting ADP-induced platelet aggregation. Although the two beta-blockers were marginally more potent than verapamil in inhibiting platelet aggregation induced by collagen, this was not statistically significant. Both propranolol and verapamil were slightly more active than carvedilol in inhibiting epinephrine-induced platelet aggregation, a trend consistent with the IC50 values. Intracellular cAMP levels decreased in platelets aggregated with ADP, epinephrine, and collagen. The inhibition of platelet aggregation with the three drugs resulted in a return of intracellular cAMP levels to basal values. Carvedilol and propranolol were of similar potency and around 1.5-3 times as potent as verapamil for all agonists. The formation of thromboxane B2, an end product of the arachidonic acid pathway, could be completely inhibited by the three drugs. Propranolol was 2.4 and 2.1 times more potent than carvedilol and verapamil when platelets were aggregated with ADP. The three drugs were found to be equally potent with respect to epinephrine-induced platelet aggregation. Carvedilol was significantly more potent than verapamil and equally potent as propranolol in collagen-aggregated platelets. Propranolol was more potent than its two competitors in inhibiting platelet aggregation and thromboxane B2 formation and restoring cAMP levels. With the exception of epinephrine-induced platelet aggregation and thromboxane formation, verapamil tended to be less potent than carvedilol.